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A multiethnic meta-analysis defined the association of rs12946942 with severe adolescent idiopathic scoliosis


Adolescent idiopathic scoliosis (AIS) is the most common type of scoliosis. Controlling its curve progression is the most important clinical task. Although recent genome-wide association studies (GWASs) identified several susceptibility loci associated with the development of AIS, the etiology of curve progression has been still unknown. Our previous GWAS has identified that rs12946942 showed significant association with severe AIS. To confirm the association, we conducted an international meta-analysis using four cohorts with different ethnicity. We analyzed 2272 severe AIS cases and 13,859 controls in total, and found the replication of significant association of rs12946942 (combined P = 7.23×10−13; odds ratio = 1.36, 95% confidence interval = 1.25−1.49). In silico analyses suggested that SOX9 is the most likely susceptibility gene for AIS curve progression in the locus.

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The authors declare that they have no conflict of interest.

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Members of the Japan Scoliosis Clinical Research Group (JSCRG) are listed below Acknowledgements.


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We are grateful to the individuals who participated in this study. We thank all participating subjects and clinical staff at collaborating institutes. We specially thank Y. Takahashi, T. Oguma and the members of Laboratory for Genotyping Development for technical assistance. This work was supported by Japan Agency for Medical Research and Development (AMED) (contract no. 18ek0109212h0002 to SI), Japan Orthopaedics and Traumatology Foundation (to KT and NO), Hong Kong Health and Medical Research Fund (HMRF No. 04152256) (to Y-QS) and the Swedish Research Council (No. K-2013-52X-22198-01-3) (to AG and PG).

Japan Scoliosis Clinical Research Group (JSCRG):

Noriaki Kawakami12, Taichi Tsuji12, Koki Uno13, Teppei Suzuki13, Manabu Ito14, Shohei Minami15, Toshiaki Kotani15, Tsuyoshi Sakuma15, Haruhisa Yanagida16, Hiroshi Taneichi17, Ikuho Yonezawa18, Hideki Sudo19, Kazuhiro Chiba20, Naobumi Hosogane21, Kotaro Nishida22, Kenichiro Kakutani22, Tsutomu Akazawa23, Takashi Kaito24, Kei Watanabe25, Katsumi Harimaya26, Yuki Taniguchi27, Hideki Shigematsu28, Satoru Demura29, Takahiro Iida30, Katsuki Kono31, Eijiro Okada2, Nobuyuki Fujita2 and Mitsuru Yagi2

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The authors declare that they have no conflict of interest.

Correspondence to Kota Watanabe or Shiro Ikegawa.

Supplementary information

Expression quantitative trait loci (eQTL) analysis for SOX9

Genotype count and Hardy-Weinberg equilibrium test of rs12946942

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